Skin permeation enhancer compositions

• US 4,973,468 A
• Filed: 03/22/1989
• Issued: 11/27/1990
• Est. Priority Date: 03/22/1989
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Cygnus Research Corporation
• Inventors: Chiang, Chia-Ming, Cleary, Gary W.
• Primary Examiner(s): Cashion, Jr., Merrell C.
• Assistant Examiner(s): HORNE, LEON
• Application Number:
  US07/327,312
• Time in Patent Office: 615 Days
• Field of Search: 424/447, 424/448, 424/449, 514/946, 514/947
• US Class Current: 424/449
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/7069 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents

Abstract

Skin permeation enhancer compositions are provided which increase the permeability of skin to transdermally administered pharmacologically active agents. The composition contains diethylene glycol monoethyl or monomethyl ether in addition to an ester component such as propylene glycol monolaurate, methyl laurate or the like. The compositions are particularly useful in conjuction with the transdermal administration of steroid drugs such as progestogens and estrogens. Methods and drug delivery systems for using the enhancer compositions are provided as well.

Claims

1. A composition of matter useful for the delivery of a pharmacologically active agent through the skin, comprising:

(a) a therapeutically effective amount of at least one pharmacologically active agent; and

(b) an amount of a permeation enhancer composition effective to enhance the penetration of said at least one pharmacologically active agent through skin, the enhancer composition comprising an ether component selected from the group consisting of diethylene glycol monoethyl ether, diethylene glycol monomethyl ether, and a mixture thereof, and an ester component given by the formula [CH₃ (CH₂)_m COO]_n R, in which m is an integer in the range of 8 to 16, n is 1 or 2, and R is a lower alkyl (C₁ -C₃) residue that is either unsubstituted or substituted with one or two hydroxyl groups, wherein the ratio of ether to ester in the enhancer composition is in the range of about 90;

10 to about 40;

60 (V/V).

2. The composition of claim 1, wherein n is 10.

3. The composition of claim 1, wherein the ether component is diethylene glycol monoethyl ether.

4. The composition of claim 2, wherein the ether component is diethylene glycol monoethyl ether.

5. The composition of claim 1, wherein the ether component is diethylene glycol monoethyl ether and the ester component comprises propylene glycol monolaurate or propylene glycol monolaurate in combination with propylene glycol dilaurate.

6. The composition of claim 1, wherein the ether component is diethylene glycol monoethyl ether and the ester component is a lower alkyl (C₁ -C₃) laurate.

7. The composition of claim 1, wherein the at least one pharmacologically active agent is a steroid.

8. The composition of claim 1, wherein the at least one pharmacologically active agent comprises a progestogen, an estrogen, or a mixture thereof.

9. The composition of claim 5, wherein the at least one pharmacologically active agent comprises a progestogen, an estrogen, or a mixture thereof.

10. The composition of claim 9, wherein the progestogen is norethindrone or norethindrone acetate, and the estrogen is estradiol.

11. The composition of claim 6, wherein the at least one pharmacologically active agent comprises a progestogen, an estrogen, or a mixture thereof.